Cancer is now the leading cause of death in the US, and breast cancer is one of the leading cancers among US women. With the dramatic growth in the older population, the absolute number of breast cancer cases diagnosed each year among women 65 and older ("older") is expected to almost double by the year 2030. Despite professional recommendations to consider chemotherapy for all women with invasive breast cancer, treatment decision making for the growing older population remains complex, largely as a result of under- representation of this group in clinical trials and the presence of competing causes of mortality, leading to persistent uncertainty about the balance of chemotherapy benefits and harms. Unfortunately, age, comorbidity and clinical judgement fail to predict which older women will tolerate chemotherapy. We have assembled a trans-disciplinary team of oncologists, geriatricians, cancer epidemiologists, health services researchers, demographers, decision scientists and consumers to fill gaps in our knowledge about chemotherapy in older women. We propose to develop and validate an index of "physiological age", defined as capacity to respond to stressors such as chemotherapy. The proposed study will be nested in a large 5- year NCI-funded prospective cohort of newly diagnosed breast cancer patients (n=5,021) enrolled in Kaiser Permanente of Northern California (KPNC). KPNC has automated, high quality databases that allow for collection of detailed chemotherapy-related information. We will enroll all women 65 and older from the cohort study and measure "physiological age" from interview and computerized records, concentrating on variables that can be readily obtained in routine practice. We will develop the index using data from a portion of the sample, then test the ability of the index to correctly predict observed toxicity outcomes in an independent sample. We will also test the ability of the index to predict 12-month quality of life and all-cause mortality. Results will then be used to enhance a widely used web-based clinical decision tool (Adjuvant!). Our approach leverages existing resources to address important new scientific questions in a cost efficient manner. This project is innovative in its focus on older women - an under-studied but growing population at risk for breast cancer - and the application of "physiological age" as a method of tailoring treatment to an individual older woman's underlying health and ability to tolerate chemotherapy. Our approach could be used to enhance the quality of shared treatment decision making between the expanding older population that will develop breast cancer and their providers. The paradigm we develop should also be broadly portable to chemotherapy decisions for other common cancers affecting older populations. [unreadable] [unreadable] [unreadable]